Metabolic, behavioural, and psychosocial risk factors and cardiovascular disease in women compared with men in 21 high-income, middle-income, and low-income countries: an analysis of the PURE study.

BACKGROUND: There is a paucity of data on the prevalence of risk factors and their associations with incident cardiovascular disease in women compared with men, especially from low-income and middle-income countries. METHODS: In the Prospective Urban Rural Epidemiological (PURE) study, we enrolled participants from the general population from 21 high-income, middle-income, and low-income countries and followed them up for approximately 10 years. We recorded information on participants' metabolic, behavioural, and psychosocial risk factors. For this analysis, we included participants aged 35-70 years at baseline without a history of cardiovascular disease, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (cardiovascular disease deaths, myocardial infarction, stroke, and heart failure). We report the prevalence of each risk factor in women and men, their hazard ratios (HRs), and population-attributable fractions (PAFs) associated with major cardiovascular disease. The PURE study is registered with ClinicalTrials.gov, NCT03225586. FINDINGS: In this analysis, we included 155 724 participants enrolled and followed-up between Jan 5, 2005, and Sept 13, 2021, (90 934 [58·4%] women and 64 790 [41·6%] men), with a median follow-up of 10·1 years (IQR 8·5-12·0). At study entry, the mean age of women was 49·8 years (SD 9·7) compared with 50·8 years (9·8) in men. As of data cutoff (Sept 13, 2021), 4280 major cardiovascular disease events had occurred in women (age-standardised incidence rate of 5·0 events [95% CI 4·9-5·2] per 1000 person-years) and 4911 in men (8·2 [8·0-8·4] per 1000 person-years). Compared with men, women presented with a more favourable cardiovascular risk profile, especially at younger ages. The HRs for metabolic risk factors were similar in women and men, except for non-HDL cholesterol, for which high non-HDL cholesterol was associated with an HR for major cardiovascular disease of 1·11 (95% CI 1·01-1·21) in women and 1·28 (1·19-1·39) in men, with a consistent pattern for higher risk among men than among women with other lipid markers. Symptoms of depression had a HR of 1·09 (0·98-1·21) in women and 1·42 (1·25-1·60) in men. By contrast, consumption of a diet with a PURE score of 4 or lower (score ranges from 0 to 8), was more strongly associated with major cardiovascular disease in women (1·17 [1·08-1·26]) than in men (1·07 [0·99-1·15]). The total PAFs associated with behavioural and psychosocial risk factors were greater in men (15·7%) than in women (8·4%) predominantly due to the larger contribution of smoking to PAFs in men (ie, 1·3% [95% CI 0·5-2·1] in women vs 10·7% [8·8-12·6] in men). INTERPRETATION: Lipid markers and depression are more strongly associated with the risk of cardiovascular disease in men than in women, whereas diet is more strongly associated with the risk of cardiovascular disease in women than in men. The similar associations of other risk factors with cardiovascular disease in women and men emphasise the importance of a similar strategy for the prevention of cardiovascular disease in men and women. FUNDING: Funding sources are listed at the end of the Article.

Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) for the diagnosis of delirium in adults in critical care settings.

BACKGROUND: Delirium is an underdiagnosed clinical syndrome typified by an acute alteration of mental state. It is an important problem in critical care and intensive care units (ICU) due to its high prevalence and its association with adverse outcomes. Delirium is a very distressing condition for patients, with a huge impact on their well-being. Diagnosis of delirium in the critical care setting is challenging. This is especially true for patients who are mechanically ventilated and are therefore unable to engage in a verbal interview. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is a tool specifically designed to assess for delirium in the context of ICU patients, including those on mechanical ventilation. CAM-ICU can be administered by non-specialists to give a dichotomous delirium present/absent result. OBJECTIVES: To determine the diagnostic accuracy of the CAM-ICU for the diagnosis of delirium in adult patients in critical care units. SEARCH METHODS: We searched MEDLINE (Ovid SP, 1946 to 8 July 2022), Embase (Ovid SP, 1982 to 8 July 2022), Web of Science Core Collection (ISI Web of Knowledge, 1945 to 8 July 2022), PsycINFO (Ovid SP, 1806 to 8 July 2022), and LILACS (BIREME, 1982 to 8 July 2022). We checked the reference lists of included studies and other resources for additional potentially relevant studies. We also searched the Health Technology Assessment database, the Cochrane Library, Aggressive Research Intelligence Facility database, WHO ICTRP, ClinicalTrials.gov, and websites of scientific associations to access any annual meetings and abstracts of conference proceedings in the field. SELECTION CRITERIA: We included diagnostic studies enrolling adult ICU patients assessed using the CAM-ICU tool, regardless of language or publication status and reporting sufficient data on delirium diagnosis for the construction of 2 x 2 tables. Eligible studies evaluated the diagnostic performance of the CAM-ICU versus a clinical reference standard based on any iteration of the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria applied by a clinical expert. DATA COLLECTION AND ANALYSIS: Two review authors independently selected and collated study data. We assessed the methodological quality of studies using the QUADAS-2 tool. We used two univariate fixed-effect or random-effects models to determine summary estimates of sensitivity and specificity. We performed sensitivity analyses that excluded studies considered to be at high risk of bias and high concerns in applicability, due mainly to the target population included (e.g. patients with traumatic brain injury). We also investigated potential sources of heterogeneity, assessing the effect of reference standard diagnosis and proportion of patients ventilated. MAIN RESULTS: We included 25 studies (2817 participants). The mean age of participants ranged from 48 to 69 years; 15 of the studies included critical care units admitting mixed populations (e.g. medical, trauma, surgery patients). The percentage of patients receiving mechanical ventilation ranged from 11.8% to 100%. The prevalence of delirium in the studies included ranged from 12.5% to 83.9%. Presence of delirium was determined by the application of DSM-IV criteria in 13 out of 25 included studies. We assessed 13 studies as at low risk of bias and low applicability concerns for all QUADAS-2 domains. The most common issue of concern was flow and timing of the tests, followed by patient selection. Overall, we estimated a pooled sensitivity of 0.78 (95% confidence interval (CI) 0.72 to 0.83) and a pooled specificity of 0.95 (95% CI 0.92 to 0.97). Sensitivity analysis restricted to studies at low risk of bias and without any applicability concerns (n = 13 studies) gave similar summary accuracy indices (sensitivity 0.80 (95% CI 0.72 to 0.86), specificity 0.95 (95% CI 0.93 to 0.97)). Subgroup analyses based on diagnostic assessment found summary estimates of sensitivity and specificity for studies using DSM-IV of 0.79 (95% CI 0.72 to 0.85) and 0.94 (95% CI 0.90 to 0.96). For studies that used DSM-5 criteria, summary estimates of sensitivity and specificity were 0.75 (95% CI 0.67 to 0.82) and 0.98 (95% CI 0.95 to 0.99). DSM criteria had no significant effect on sensitivity (P = 0.421), but the specificity for detection of delirium was higher when DSM-5 criteria were used (P = 0.024). The relative specificity comparing DSM-5 versus DSM-IV criteria was 1.05 (95% CI 1.02 to 1.08). Summary estimates of sensitivity and specificity for studies recruiting < 100% of patients with mechanical ventilation were 0.81 (95% CI 0.75 to 0.85) and 0.95 (95% CI 0.91 to 0.98). For studies that exclusively recruited patients with mechanical ventilation, summary estimates of sensitivity and specificity were 0.91 (95% CI 0.76 to 0.97) and 0.98 (95% CI 0.92 to 0.99). Although there was a suggestion of differential performance of CAM-ICU in ventilated patients, the differences were not significant in sensitivity (P = 0.316) or in specificity (P = 0.493). AUTHORS' CONCLUSIONS: The CAM-ICU tool may have a role in the early identification of delirium, in adult patients hospitalized in intensive care units, including those on mechanical ventilation, when non-specialized, properly trained clinical personnel apply the CAM-ICU. The test is most useful for exclusion of delirium. The test may miss a proportion of patients with incident delirium, therefore in situations where detection of all delirium cases is desirable, it may be best to repeat the test or combine CAM-ICU with another assessment. Future studies should compare different screening tests proposed for bedside assessment of delirium, as this approach will reveal which tool yields superior accuracy. In addition, future studies should consider and report the flow and timing of the tests and clearly report key characteristics related to patient selection. Finally, future research should focus on the impact of CAM-ICU screening on patient outcomes.

Impact of structural-level environmental interventions on physical activity: a systematic review.

OBJECTIVE: To determine the effectiveness of structural-level environmental interventions on the changes in PA levels in the populations examined. METHODS: Natural experiments that involve environmental intervention with structural modification were included. The primary outcome PA levels with consideration of both objective and subjective measurements. An electronic search was carried out in Medline/Pubmed, SCIENCE DIRECT, WEB OF SCIENCE, and CINAHL up to January 2022. Two reviewers screened titles and abstracts, selected studies, extracted relevant data, and examined study quality. A qualitative synthesis was performed. RESULTS: Twenty-six articles were included. The structural-level environmental interventions included 4 fundamental areas: schools, work environments, streets or cities, and neighborhoods or parks. Of the 26 studies, 21 examined outdoor environments like parks, cities, pedestrian walkways, or steps, while 5 examined indoor or closed environments like schools and workplaces revealing that structural-level environmental interventions improve PA levels with the greatest effect in parks and active transportation. A risk of bias is inherent in natural experiments which is a limitation of this study. In schools and work areas, there is evidence of both decrease in sedentary time and an increase in PA related to environmental modifications. CONCLUSION: Structural-level environmental modifications in parks and active transportation demonstrated greater effects in promoting PA. Environmental modifications can impact physical activity in the population. Given that the economic and cultural setting is a key variable when considering the effectiveness of structural interventions, and since only 1 of the 26 reviewed articles included such data, more studies examining economic factors are needed especially in low- and middle-income countries like in South America. TRIAL REGISTRATION: PROSPERO CRD42021229718.

Risk factors, cardiovascular disease, and mortality in South America: a PURE substudy.

AIMS: In a multinational South American cohort, we examined variations in CVD incidence and mortality rates between subpopulations stratified by country, by sex and by urban or rural location. We also examined the contributions of 12 modifiable risk factors to CVD development and to death. METHODS AND RESULTS: This prospective cohort study included 24 718 participants from 51 urban and 49 rural communities in Argentina, Brazil, Chile, and Colombia. The mean follow-up was 10.3 years. The incidence of CVD and mortality rates were calculated for the overall cohort and in subpopulations. Hazard ratios and population attributable fractions (PAFs) for CVD and for death were examined for 12 common modifiable risk factors, grouped as metabolic (hypertension, diabetes, abdominal obesity, and high non-HDL cholesterol), behavioural (tobacco, alcohol, diet quality, and physical activity), and others (education, household air pollution, strength, and depression). Leading causes of death were CVD (31.1%), cancer (30.6%), and respiratory diseases (8.6%). The incidence of CVD (per 1000 person-years) only modestly varied between countries, with the highest incidence in Brazil (3.86) and the lowest in Argentina (3.07). There was a greater variation in mortality rates (per 1000 person-years) between countries, with the highest in Argentina (5.98) and the lowest in Chile (4.07). Men had a higher incidence of CVD (4.48 vs. 2.60 per 1000 person-years) and a higher mortality rate (6.33 vs. 3.96 per 1000 person-years) compared with women. Deaths were higher in rural compared to urban areas. Approximately 72% of the PAF for CVD and 69% of the PAF for deaths were attributable to 12 modifiable risk factors. For CVD, largest PAFs were due to hypertension (18.7%), abdominal obesity (15.4%), tobacco use (13.5%), low strength (5.6%), and diabetes (5.3%). For death, the largest PAFs were from tobacco use (14.4%), hypertension (12.0%), low education (10.5%), abdominal obesity (9.7%), and diabetes (5.5%). CONCLUSIONS: Cardiovascular disease, cancer, and respiratory diseases account for over two-thirds of deaths in South America. Men have consistently higher CVD and mortality rates than women. A large proportion of CVD and premature deaths could be averted by controlling metabolic risk factors and tobacco use, which are common leading risk factors for both outcomes in the region.

Differences in Bacterial Small RNAs in Stool Samples from Hypercholesterolemic and Normocholesterolemic Subjects.

Cholesterol metabolism is important at the physiological level as well as in several diseases, with small RNA being an element to consider in terms of its epigenetic control. Thus, the aim of this study was to identify differences between bacterial small RNAs present at the gut level in hypercholesterolemic and normocholesterolemic individuals. Twenty stool samples were collected from hypercholesterolemic and normocholesterolemic subjects. RNA extraction and small RNA sequencing were performed, followed by bioinformatics analyses with BrumiR, Bowtie 2, BLASTn, DESeq2, and IntaRNA, after the filtering of the reads with fastp. In addition, the prediction of secondary structures was obtained with RNAfold WebServer. Most of the small RNAs were of bacterial origin and presented a greater number of readings in normocholesterolemic participants. The upregulation of small RNA ID 2909606 associated with Coprococcus eutactus (family Lachnospiraceae) was presented in hypercholesterolemic subjects. In addition, a positive correlation was established between small RNA ID 2149569 from the species Blautia wexlerae and hypercholesterolemic subjects. Other bacterial and archaeal small RNAs that interacted with the LDL receptor (LDLR) were identified. For these sequences, the prediction of secondary structures was also obtained. There were significant differences in bacterial small RNAs associated with cholesterol metabolism in hypercholesterolemic and normocholesterolemic participants.

Effectiveness of Respiratory Muscle Training in Adults With Pulmonary Hypertension. A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with pulmonary hypertension (PH) may have impaired exercise capacity and quality of life; this may possibly be due to the early onset of dyspnoea associated with respiratory muscle weakness. Respiratory muscle training could improve the condition of these patients, so this study aimed to determine, through a systematic review and meta-analysis, the effectiveness of respiratory muscle training in adult patients with PH. METHODS: Medline, Embase, CENTRAL, clinical trial registries databases, and grey literature and reference lists of reviews related to the objective were searched up to March 2022. Controlled clinical trials comparing the effectiveness of respiratory muscle training with sham or no intervention in adults with PH were included. Records were independently screened by two authors. The primary outcomes were maximal and functional exercise capacity, quality of life, and dyspnoea. The secondary outcomes were respiratory muscle strength, physical activity, lung function, and adverse events. Two authors independently extracted data and the study quality was assessed using the Cochrane risk-of-bias tool 2 (RoB 2). The certainty of the evidence was assessed according to the GRADE approach. RESULTS: A total of 5,524 records were screened, and seven randomised clinical trials (RCTs) (257 participants) were included. It was uncertain whether inspiratory muscle training (IMT), compared with sham IMT or no intervention, increased the distance walked in the 6-minute walk test (6MWT) (MD, 39 m; 95% CI, 20.72-57.39; I2=27%; four RCTs; very low certainty of evidence) and slightly decreased the perceived sensation of dyspnoea (MD, 0.5 points on the mMRC scale; 95% CI, -0.87 to -0.13; I2=0%; two RCTs; very low certainty of evidence). In addition, it was uncertain whether IMT had no effect on the emotional (SMD, -0.34; 95% CI, -1.06 to 0.38; I2=64%; three RCTs; very low certainty of evidence) and physical (SMD, 0.06; 95% CI, -0.41 to 0.52; I2=16%; three RCTs; very low certainty of evidence) component of quality of life. CONCLUSIONS: It is uncertain whether IMT increases functional exercise capacity and slightly decreases the sensation of dyspnoea. In addition, it is uncertain whether IMT does not affect the quality of life. More RCTs and with a better methodological design are needed to increase the certainty of the evidence and determine the real effect of this intervention.

Personal and household PM2.5 and black carbon exposure measures and respiratory symptoms in 8 low- and middle-income countries.

BACKGROUND: Household air pollution (HAP) from cooking with solid fuels has been associated with adverse respiratory effects, but most studies use surveys of fuel use to define HAP exposure, rather than on actual air pollution exposure measurements. OBJECTIVE: To examine associations between household and personal fine particulate matter (PM2.5) and black carbon (BC) measures and respiratory symptoms. METHODS: As part of the Prospective Urban and Rural Epidemiology Air Pollution study, we analyzed 48-h household and personal PM2.5 and BC measurements for 870 individuals using different cooking fuels from 62 communities in 8 countries (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Self-reported respiratory symptoms were collected after monitoring. Associations between PM2.5 and BC exposures and respiratory symptoms were examined using logistic regression models, controlling for individual, household, and community covariates. RESULTS: The median (interquartile range) of household and personal PM2.5 was 73.5 (119.1) and 65.3 (91.5) µg/m3, and for household and personal BC was 3.4 (8.3) and 2.5 (4.9) x10-5 m-1, respectively. We observed associations between household PM2.5 and wheeze (OR: 1.25; 95%CI: 1.07, 1.46), cough (OR: 1.22; 95%CI: 1.06, 1.39), and sputum (OR: 1.26; 95%CI: 1.10, 1.44), as well as exposure to household BC and wheeze (OR: 1.20; 95%CI: 1.03, 1.39) and sputum (OR: 1.20; 95%CI: 1.05, 1.36), per IQR increase. We observed associations between personal PM2.5 and wheeze (OR: 1.23; 95%CI: 1.00, 1.50) and sputum (OR: 1.19; 95%CI: 1.00, 1.41). For household PM2.5 and BC, associations were generally stronger for females compared to males. Models using an indicator variable of solid versus clean fuels resulted in larger OR estimates with less precision. CONCLUSIONS: We used measurements of household and personal air pollution for individuals using different cooking fuels and documented strong associations with respiratory symptoms.

Implementation of physiotherapy telerehabilitation before and post Covid-19 outbreak: A comparative narrative between South American countries and Australia.

The continuous development in telecommunication tech-nologies has created opportunities for health professionals to optimise healthcare delivery by adopting digital tools into rehabilitation programs (i.e., telerehabilitation). These tech-nological advances, along with the demographic and social characteristics of each country, have made the implementa-tion of telerehabilitation a disparate process across regions. We have gathered the experience of four countries (Australia, Chile, Brazil, and Colombia) in two different regions (Ocea-nia and South America) to recompile the history pre- and post-Covid-19 outbreak until January of 2021, the barriers to, and facilitators of telerehabilitation, and outline the future challenges for these countries.

Dietary patterns and blood pressure in Southern Cone of Latin America.

BACKGROUND AND AIMS: in the Southern Cone of Latin America, previous studies have shown that blood hypertension is one of the most significant risk factor for cardiovascular disease, and diet plays a fundamental role. We analyzed the cross-sectional relationship between dietary patterns (DP) and blood pressure values in people involved in the CESCAS I Study. METHODS AND RESULTS: the participants (n = 4626) were derived from randomly selected samples in 4 cities (Bariloche and Marcos Paz, Argentina; Temuco, Chile; and Pando-Barros Blancos, Uruguay). To define DP, a food-frequency questionnaire was applied and principal component analysis was performed. Blood pressure was determined according to standardized guidelines. A multivariate regression model was developed to determine the association between each DP and blood pressure values, according to the quartile (Q) of adherence to DP. Two predominant DP were detected, Prudent (PDP, higher consumption of fruits, vegetables, legumes, whole grains, fish, seafood and nuts) and Western (WDP, higher consumption of red and processed meats, dressings, sweets, snacks and refined grains). A significant inverse association was found between adherence to PDP and systolic and diastolic blood pressure (-1.85 and -1.29 mmHg for Q4 vs Q1, respectively). Adherence to WDP was positively associated with systolic blood pressure (2.09 mmHg for Q4 vs Q1). CONCLUSION: the WDP detected in the studied population is positively associated with higher levels of blood pressure, while greater adherence to healthy DP has a positive impact on blood pressure.

Exercise training for adult lung transplant recipients.

BACKGROUND: Pulmonary transplantation is the final treatment option for people with end-stage respiratory diseases. Evidence suggests that exercise training may contribute to speeding up physical recovery in adults undergoing lung transplantation, helping to minimize or resolve impairments due to physical inactivity in both the pre- and post-transplant stages. However, there is a lack of detailed guidelines on how exercise training should be carried out in this specific sub-population. OBJECTIVES: To determine the benefits and safety of exercise training in adult patients who have undergone lung transplantation, measuring the maximal and functional exercise capacity; health-related quality of life; adverse events; patient readmission; pulmonary function; muscular strength; pathological bone fractures; return to normal activities and death. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register up to 6 October 2020 using relevant search terms for this review. Studies in the CKTR are identified through CENTRAL, MEDLINE, and EMBASE searches, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) were included comparing exercise training with usual care or no exercise training, or with another exercise training program in terms of dosage, modality, program length, or use of supporting exercise devices. The study population comprised of participants older than 18 years who underwent lung transplantation independent of their underlying respiratory pathology. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed all records identified by the search strategy and selected studies that met the eligibility criteria for inclusion in this review. In the first instance, the disagreements were resolved by consensus, and if this was not possible the decision was taken by a third reviewer. The same reviewers independently extracted outcome data from included studies and assessed risk of bias. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Eight RCTs (438 participants) were included in this review. The median sample size was 60 participants with a range from 16 to 83 participants. The mean age of participants was 54.9 years and 51.9% of the participants were male. The median duration of the exercise training programs for the groups undergoing the intervention was 13 weeks, and the median duration of training in the active control groups was four weeks. Overall the risk of bias was considered to be high, mainly due to the inability to blind the study participants and the selective reporting of the results. Due to small number of studies included in this review, and the heterogeneity of the intervention and outcomes, we did not obtain a summary estimate of the results. Two studies comparing resistance exercise training with no exercise reported increases in muscle strength and bone mineral density (surrogate outcomes for pathological bone fractures) with exercise training (P > 0.05), but no differences in adverse events. Exercise capacity, health-related quality of life (HRQoL), pulmonary function, and death (any cause) were not reported. Three studies compared two different resistant training programs. Two studies comparing squats using a vibration platform (WBVT) compared to squats on the floor reported an improvement in 6-minute walk test (6MWT) (28.4 metres, 95% CI 3 to 53.7; P = 0.029; and 28.3 metres, 95% CI 10.0 to 46.6; P < 0.05) with the WBVT. Supervised upper limb exercise (SULP) program improved 6MWT at 6 months compared to no supervised upper limb exercise (NULP) (SULP group: 561.2 ± 83.6 metres; NULP group: 503.5 ± 115.2 metres; P = 0.01). There were no differences in HRQoL, adverse events, muscular strength, or death (any cause). Pulmonary function and pathological bone fractures were not reported. Two studies comparing multimodal exercise training with no exercise reported improvement in 6MWT at 3 months (P = 0.008) and at 12-months post-transplant (P = 0.002) and muscular strength (quadriceps force (P = 0.001); maximum leg press (P = 0.047)) with multimodal exercise, but no improvement in HRQoL, adverse events, pulmonary function, pathological bone fractures (lumbar T-score), or death (any cause). One study comparing the same multimodal exercise programs given over 7 and 14 weeks reported no differences in 6MWT, HRQoL, adverse events, pulmonary function, muscle strength, or death (any cause). Pathological bone fractures were not reported. According to GRADE criteria, we rated the certainty of the evidence as very low, mainly due to the high risk of bias and serious imprecision. AUTHORS' CONCLUSIONS: In adults undergoing lung transplantation the evidence about the effects of exercise training is very uncertain in terms of maximal and functional exercise capacity, HRQoL and safety, due to very imprecise estimates of effects and high risk of bias.

Association of estimated sleep duration and naps with mortality and cardiovascular events: a study of 116 632 people from 21 countries.

AIMS: To investigate the association of estimated total daily sleep duration and daytime nap duration with deaths and major cardiovascular events. METHODS AND RESULTS: We estimated the durations of total daily sleep and daytime naps based on the amount of time in bed and self-reported napping time and examined the associations between them and the composite outcome of deaths and major cardiovascular events in 116 632 participants from seven regions. After a median follow-up of 7.8 years, we recorded 4381 deaths and 4365 major cardiovascular events. It showed both shorter (≤6 h/day) and longer (>8 h/day) estimated total sleep durations were associated with an increased risk of the composite outcome when adjusted for age and sex. After adjustment for demographic characteristics, lifestyle behaviours and health status, a J-shaped association was observed. Compared with sleeping 6-8 h/day, those who slept ≤6 h/day had a non-significant trend for increased risk of the composite outcome [hazard ratio (HR), 1.09; 95% confidence interval, 0.99-1.20]. As estimated sleep duration increased, we also noticed a significant trend for a greater risk of the composite outcome [HR of 1.05 (0.99-1.12), 1.17 (1.09-1.25), and 1.41 (1.30-1.53) for 8-9 h/day, 9-10 h/day, and >10 h/day, Ptrend < 0.0001, respectively]. The results were similar for each of all-cause mortality and major cardiovascular events. Daytime nap duration was associated with an increased risk of the composite events in those with over 6 h of nocturnal sleep duration, but not in shorter nocturnal sleepers (≤6 h). CONCLUSION: Estimated total sleep duration of 6-8 h per day is associated with the lowest risk of deaths and major cardiovascular events. Daytime napping is associated with increased risks of major cardiovascular events and deaths in those with >6 h of nighttime sleep but not in those sleeping ≤6 h/night.

The effect of physical activity on mortality and cardiovascular disease in 130 000 people from 17 high-income, middle-income, and low-income countries: the PURE study.

BACKGROUND: Physical activity has a protective effect against cardiovascular disease (CVD) in high-income countries, where physical activity is mainly recreational, but it is not known if this is also observed in lower-income countries, where physical activity is mainly non-recreational. We examined whether different amounts and types of physical activity are associated with lower mortality and CVD in countries at different economic levels. METHODS: In this prospective cohort study, we recruited participants from 17 countries (Canada, Sweden, United Arab Emirates, Argentina, Brazil, Chile, Poland, Turkey, Malaysia, South Africa, China, Colombia, Iran, Bangladesh, India, Pakistan, and Zimbabwe). Within each country, urban and rural areas in and around selected cities and towns were identified to reflect the geographical diversity. Within these communities, we invited individuals aged between 35 and 70 years who intended to live at their current address for at least another 4 years. Total physical activity was assessed using the International Physical Activity Questionnaire (IPQA). Participants with pre-existing CVD were excluded from the analyses. Mortality and CVD were recorded during a mean of 6·9 years of follow-up. Primary clinical outcomes during follow-up were mortality plus major CVD (CVD mortality, incident myocardial infarction, stroke, or heart failure), either as a composite or separately. The effects of physical activity on mortality and CVD were adjusted for sociodemographic factors and other risk factors taking into account household, community, and country clustering. FINDINGS: Between Jan 1, 2003, and Dec 31, 2010, 168 916 participants were enrolled, of whom 141 945 completed the IPAQ. Analyses were limited to the 130 843 participants without pre-existing CVD. Compared with low physical activity (<600 metabolic equivalents [MET] × minutes per week or <150 minutes per week of moderate intensity physical activity), moderate (600-3000 MET × minutes or 150-750 minutes per week) and high physical activity (>3000 MET × minutes or >750 minutes per week) were associated with graded reduction in mortality (hazard ratio 0·80, 95% CI 0·74-0·87 and 0·65, 0·60-0·71; p<0·0001 for trend), and major CVD (0·86, 0·78-0·93; p<0·001 for trend). Higher physical activity was associated with lower risk of CVD and mortality in high-income, middle-income, and low-income countries. The adjusted population attributable fraction for not meeting the physical activity guidelines was 8·0% for mortality and 4·6% for major CVD, and for not meeting high physical activity was 13·0% for mortality and 9·5% for major CVD. Both recreational and non-recreational physical activity were associated with benefits. INTERPRETATION: Higher recreational and non-recreational physical activity was associated with a lower risk of mortality and CVD events in individuals from low-income, middle-income, and high-income countries. Increasing physical activity is a simple, widely applicable, low cost global strategy that could reduce deaths and CVD in middle age. FUNDING: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Ontario SPOR Support Unit, Ontario Ministry of Health and Long-Term Care, AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, GSK, Novartis, King Pharma, and national and local organisations in participating countries that are listed at the end of the Article.

Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study.

BACKGROUND: The relationship between macronutrients and cardiovascular disease and mortality is controversial. Most available data are from European and North American populations where nutrition excess is more likely, so their applicability to other populations is unclear. METHODS: The Prospective Urban Rural Epidemiology (PURE) study is a large, epidemiological cohort study of individuals aged 35-70 years (enrolled between Jan 1, 2003, and March 31, 2013) in 18 countries with a median follow-up of 7·4 years (IQR 5·3-9·3). Dietary intake of 135 335 individuals was recorded using validated food frequency questionnaires. The primary outcomes were total mortality and major cardiovascular events (fatal cardiovascular disease, non-fatal myocardial infarction, stroke, and heart failure). Secondary outcomes were all myocardial infarctions, stroke, cardiovascular disease mortality, and non-cardiovascular disease mortality. Participants were categorised into quintiles of nutrient intake (carbohydrate, fats, and protein) based on percentage of energy provided by nutrients. We assessed the associations between consumption of carbohydrate, total fat, and each type of fat with cardiovascular disease and total mortality. We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random intercepts to account for centre clustering. FINDINGS: During follow-up, we documented 5796 deaths and 4784 major cardiovascular disease events. Higher carbohydrate intake was associated with an increased risk of total mortality (highest [quintile 5] vs lowest quintile [quintile 1] category, HR 1·28 [95% CI 1·12-1·46], ptrend=0·0001) but not with the risk of cardiovascular disease or cardiovascular disease mortality. Intake of total fat and each type of fat was associated with lower risk of total mortality (quintile 5 vs quintile 1, total fat: HR 0·77 [95% CI 0·67-0·87], ptrend<0·0001; saturated fat, HR 0·86 [0·76-0·99], ptrend=0·0088; monounsaturated fat: HR 0·81 [0·71-0·92], ptrend<0·0001; and polyunsaturated fat: HR 0·80 [0·71-0·89], ptrend<0·0001). Higher saturated fat intake was associated with lower risk of stroke (quintile 5 vs quintile 1, HR 0·79 [95% CI 0·64-0·98], ptrend=0·0498). Total fat and saturated and unsaturated fats were not significantly associated with risk of myocardial infarction or cardiovascular disease mortality. INTERPRETATION: High carbohydrate intake was associated with higher risk of total mortality, whereas total fat and individual types of fat were related to lower total mortality. Total fat and types of fat were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality, whereas saturated fat had an inverse association with stroke. Global dietary guidelines should be reconsidered in light of these findings. FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).

Estimating prevalence of chronic obstructive pulmonary disease in the Southern Cone of Latin America: how different spirometric criteria may affect disease burden and health policies.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide. The study aimed to determine and compare the prevalence of COPD in the general population aged 45-74 years old according to fixed ratio and lower limit of normal (LLN) thresholds in four cities in the Southern Cone of Latin America. METHODS: The Pulmonary Risk in South America (PRISA) study used a 4-stage stratified sampling method to select 5814 participants from 4 cities in the Southern Cone of Latin America (Bariloche and Marcos Paz, Argentina; Temuco, Chile; and Pando-Barros Blancos, Uruguay). Data on demographic information, medical history, risk factors, pre-bronchodilator and post-bronchodilator spirometry were obtained using a standard protocol. According to GOLD, COPD was defined as a post-bronchodilator ratio of forced expiratory volume in one second (FEV1) over forced vital capacity (FVC) less than 70%. The LLN threshold was defined as the lower fifth percentile for predicted FEV1/FVC, and was evaluated as an alternative COPD definition. RESULTS: Overall COPD prevalence was 9.3% (95% CI 8.4, 10.2%), and men had a higher prevalence [11.8% (95% CI 10.3, 13.3%)] than women [7.3% (95% CI 6.2, 8.3%)] with the fixed ratio. Overall COPD prevalence using LLN was 4.7% (95% CI 4.1, 5.3%), higher in men: 5.8% (95% CI 4.7, 6.8%) than women: 3.9% (95% CI 3.1, 4.7%). COPD prevalence was significantly higher among those who were older, had

Efficacy, safety and effectiveness of licensed rotavirus vaccines: a systematic review and meta-analysis for Latin America and the Caribbean.

BACKGROUND: RotaTeq™ (RV5; Merck & Co. Inc., USA) and Rotarix™ (RV1, GlaxoSmithKline, Belgium) vaccines, developed to prevent rotavirus diarrhea in children under five years old, were both introduced into national immunization programs in 2006. As many countries in Latin America and the Caribbean have included either RV5 or RV1 in their routine childhood vaccination programs, we conducted a systematic review and meta-analysis to analyze efficacy, safety and effectiveness data from the region. METHODS: We conducted a systematic search in PubMed, EMBASE, Scielo, Lilacs and the Cochrane Central Register, for controlled efficacy, safety and effectiveness studies published between January 2000 until December 2011, on RV5 and RV1 across Latin America (where both vaccines are available since 2006). The primary outcome measures were: rotavirus-related gastroenteritis of any severity; rotavirus emergency department visits and hospitalization; and severe adverse events. RESULTS: The results of the meta-analysis for efficacy show that RV1 reduced the risk of any-severity rotavirus-related gastroenteritis by 65% (relative risk (RR) 0.35, 95% confidence interval (CI) 0.25; 0.50), and of severe gastroenteritis by 82% (RR 0.18, 95%CI 0.12; 0.26) versus placebo. In trials, both vaccines significantly reduced the risk of hospitalization and emergency visits by 85% (RR 0.15, 95%CI 0.09; 0.25) for RV1 and by 90% (RR 0.099, 95%CI 0.012; 0.77) for RV5. Vaccination with RV5 or RV1 did not increase the risk of death, intussusception, or other severe adverse events which were previously associated with the first licensed rotavirus vaccine. Real-world effectiveness studies showed that both vaccines reduced rotavirus hospitalization in the region by around 45-50% for RV5 (for 1 to 3 doses, respectively), and, by around 50-80% for RV1 (for 1 to 2 doses, respectively). For RV1, effectiveness against hospitalization was highest (around 80-96%) for children vaccinated before 12 months of age, compared with 5-60% effectiveness in older children. Both vaccines were most effective in preventing more severe gastroenteritis (70% for RV5 and 80-90% for RV1) and severe gastroenteritis (50% for RV5 and 70-80% for RV1). CONCLUSION: This systematic literature review confirms rotavirus vaccination has been proven effective and well tolerated in protecting children in Latin America and the Caribbean.

Alcohol consumption and cardiovascular disease, cancer, injury, admission to hospital, and mortality: a prospective cohort study.

BACKGROUND: Alcohol consumption is proposed to be the third most important modifiable risk factor for death and disability. However, alcohol consumption has been associated with both benefits and harms, and previous studies were mostly done in high-income countries. We investigated associations between alcohol consumption and outcomes in a prospective cohort of countries at different economic levels in five continents. METHODS: We included information from 12 countries participating in the Prospective Urban Rural Epidemiological (PURE) study, a prospective cohort study of individuals aged 35-70 years. We used Cox proportional hazards regression to study associations with mortality (n=2723), cardiovascular disease (n=2742), myocardial infarction (n=979), stroke (n=817), alcohol-related cancer (n=764), injury (n=824), admission to hospital (n=8786), and for a composite of these outcomes (n=11,963). FINDINGS: We included 114,970 adults, of whom 12,904 (11%) were from high-income countries (HICs), 24,408 (21%) were from upper-middle-income countries (UMICs), 48,845 (43%) were from lower-middle-income countries (LMICs), and 28,813 (25%) were from low-income countries (LICs). Median follow-up was 4.3 years (IQR 3.0-6.0). Current drinking was reported by 36,030 (31%) individuals, and was associated with reduced myocardial infarction (hazard ratio [HR] 0.76 [95% CI 0.63-0.93]), but increased alcohol-related cancers (HR 1.51 [1.22-1.89]) and injury (HR 1.29 [1.04-1.61]). High intake was associated with increased mortality (HR 1.31 [1.04-1.66]). Compared with never drinkers, we identified significantly reduced hazards for the composite outcome for current drinkers in HICs and UMICs (HR 0.84 [0.77-0.92]), but not in LMICs and LICs, for which we identified no reductions in this outcome (HR 1.07 [0.95-1.21]; pinteraction<0.0001). INTERPRETATION: Current alcohol consumption had differing associations by clinical outcome, and differing associations by income region. However, we identified sufficient commonalities to support global health strategies and national initiatives to reduce harmful alcohol use. FUNDING: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.

Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study.

BACKGROUND: Reduced muscular strength, as measured by grip strength, has been associated with an increased risk of all-cause and cardiovascular mortality. Grip strength is appealing as a simple, quick, and inexpensive means of stratifying an individual's risk of cardiovascular death. However, the prognostic value of grip strength with respect to the number and range of populations and confounders is unknown. The aim of this study was to assess the independent prognostic importance of grip strength measurement in socioculturally and economically diverse countries. METHODS: The Prospective Urban-Rural Epidemiology (PURE) study is a large, longitudinal population study done in 17 countries of varying incomes and sociocultural settings. We enrolled an unbiased sample of households, which were eligible if at least one household member was aged 35-70 years and if household members intended to stay at that address for another 4 years. Participants were assessed for grip strength, measured using a Jamar dynamometer. During a median follow-up of 4.0 years (IQR 2.9-5.1), we assessed all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, myocardial infarction, stroke, diabetes, cancer, pneumonia, hospital admission for pneumonia or chronic obstructive pulmonary disease (COPD), hospital admission for any respiratory disease (including COPD, asthma, tuberculosis, and pneumonia), injury due to fall, and fracture. Study outcomes were adjudicated using source documents by a local investigator, and a subset were adjudicated centrally. FINDINGS: Between January, 2003, and December, 2009, a total of 142,861 participants were enrolled in the PURE study, of whom 139,691 with known vital status were included in the analysis. During a median follow-up of 4.0 years (IQR 2.9-5.1), 3379 (2%) of 139,691 participants died. After adjustment, the association between grip strength and each outcome, with the exceptions of cancer and hospital admission due to respiratory illness, was similar across country-income strata. Grip strength was inversely associated with all-cause mortality (hazard ratio per 5 kg reduction in grip strength 1.16, 95% CI 1.13-1.20; p<0.0001), cardiovascular mortality (1.17, 1.11-1.24; p<0.0001), non-cardiovascular mortality (1.17, 1.12-1.21; p<0.0001), myocardial infarction (1.07, 1.02-1.11; p=0.002), and stroke (1.09, 1.05-1.15; p<0.0001). Grip strength was a stronger predictor of all-cause and cardiovascular mortality than systolic blood pressure. We found no significant association between grip strength and incident diabetes, risk of hospital admission for pneumonia or COPD, injury from fall, or fracture. In high-income countries, the risk of cancer and grip strength were positively associated (0.916, 0.880-0.953; p<0.0001), but this association was not found in middle-income and low-income countries. INTERPRETATION: This study suggests that measurement of grip strength is a simple, inexpensive risk-stratifying method for all-cause death, cardiovascular death, and cardiovascular disease. Further research is needed to identify determinants of muscular strength and to test whether improvement in strength reduces mortality and cardiovascular disease. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).

Assessing global risk factors for non-fatal injuries from road traffic accidents and falls in adults aged 35-70†years in 17 countries: a cross-sectional analysis of the Prospective Urban Rural Epidemiological (PURE) study.

OBJECTIVES: To assess risk factors associated with non-fatal injuries (NFIs) from road traffic accidents (RTAs) or falls. METHODS: Our study included 151 609 participants from the Prospective Urban Rural Epidemiological study. Participants reported whether they experienced injuries within the past 12 months that limited normal activities. Additional questions elicited data on risk factors. We employed multivariable logistic regression to analyse data. RESULTS: Overall, 5979 participants (3.9% of 151 609) reported at least one NFI. Total number of NFIs was 6300: 1428 were caused by RTAs (22.7%), 1948 by falls (30.9%) and 2924 by other causes (46.4%). Married/common law status was associated with fewer falls, but not with RTA. Age 65-70 years was associated with fewer RTAs, but more falls; age 55-64 years was associated with more falls. Male versus female was associated with more RTAs and fewer falls. In lower-middle-income countries, rural residence was associated with more RTAs and falls; in low-income countries, rural residence was associated with fewer RTAs. Previous alcohol use was associated with more RTAs and falls; current alcohol use was associated with more falls. Education was not associated with either NFI type. CONCLUSIONS: This study of persons aged 35-70 years found that some risk factors for NFI differ according to whether the injury is related to RTA or falls. Policymakers may use these differences to guide the design of prevention policies for RTA-related or fall-related NFI.

The environmental profile of a community's health: a cross-sectional study on tobacco marketing in 16 countries.

OBJECTIVE: To examine and compare tobacco marketing in 16 countries while the Framework Convention on Tobacco Control requires parties to implement a comprehensive ban on such marketing. METHODS: Between 2009 and 2012, a kilometre-long walk was completed by trained investigators in 462 communities across 16 countries to collect data on tobacco marketing. We interviewed community members about their exposure to traditional and non-traditional marketing in the previous six months. To examine differences in marketing between urban and rural communities and between high-, middle- and low-income countries, we used multilevel regression models controlling for potential confounders. FINDINGS: Compared with high-income countries, the number of tobacco advertisements observed was 81 times higher in low-income countries (incidence rate ratio, IRR: 80.98; 95% confidence interval, CI: 4.15-1578.42) and the number of tobacco outlets was 2.5 times higher in both low- and lower-middle-income countries (IRR: 2.58; 95% CI: 1.17-5.67 and IRR: 2.52; CI: 1.23-5.17, respectively). Of the 11,842 interviewees, 1184 (10%) reported seeing at least five types of tobacco marketing. Self-reported exposure to at least one type of traditional marketing was 10 times higher in low-income countries than in high-income countries (odds ratio, OR: 9.77; 95% CI: 1.24-76.77). For almost all measures, marketing exposure was significantly lower in the rural communities than in the urban communities. CONCLUSION: Despite global legislation to limit tobacco marketing, it appears ubiquitous. The frequency and type of tobacco marketing varies on the national level by income group and by community type, appearing to be greatest in low-income countries and urban communities.